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Background: Increased oxidative stress and vascular inflammation have been demonstrated in patients with cardiac syndrome X (CSX).Bilirubin, once considered simply the metabolic end product of heme degradation, has emerged as a potential endogenous inhibitor of atherosclerosis.Objective: This study was conducted to evaluate the prognostic role of serum bilirubin in disease progression and clinical outcome in patients with CSX.Methods: A total of 108 consecutive CSX patients were enrolled.Serum bilirubin levels were examined from blood samples collected before coronary angiography.All patients were prospectively followed up for 5 years.The primary end point was the combined occurrence of major adverse cardiovascular events (MACE) including cardiovascular and noncardiac death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, rehospitalization for unstable angina, and coronary revascularization.Results: There were 20 MACEs including 5 ischemic stroke, 5 noncardiac death, and 10 rehospitalization for unstable angina during follow-up.Patients with MACE had lower baseline serum bilirubin levels (P<0.001).All patients were stratified into the high-, normal-, and low-bilirubin group.The patients in high-bilirubin group had the lowest incidence of MACE (P=0.008).In a multivariate Cox regression analysis, serum bilirubin, in addition to age and basal superoxide generation of circulating mononuclear cells, was also an independent predictor of MACE (HR, 0.002; 95% CI, 0.000 to 0.520; P=0.028).Conclusions: In patients with CSX, baseline serum bilirubin level was associated with long-term outcomes.Serum bilirubin could be a predictive and protective biomarker for disease progression and the development of cardiovascular events in CSX patients.